ArticleNeoplasia (New York, N.Y.)2015
Wnt/β-Catenin Signaling Activation beyond Robust Nuclear β-Catenin Accumulation in Nondysplastic Barrett's Esophagus: Regulation via Dickkopf-1.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- DP103 as a critical modulator of Wnt signaling and cancer stemness: implications for precision treatment in triple negative breast cancer.Cell death & disease · 2026Article
- The Interplay Between Esophageal Adenocarcinoma and Its Tumor Microenvironment: Toward Innovative Therapies.Cells · 2025Review
- The Potential Role ofMicroorganisms · 2025Review
- DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target.Diagnostics (Basel, Switzerland) · 2025Review
- Article
- Esophageal carcinoma: Towards targeted therapies.Cellular oncology (Dordrecht, Netherlands) · 2020Review
- From genetics to signaling pathways: molecular pathogenesis of esophageal adenocarcinoma.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett's sequence.BMC gastroenterology · 2019Article
- Dickkopf-1 (DKK1) promotes tumor growth via Akt-phosphorylation and independently of Wnt-axis in Barrett's associated esophageal adenocarcinoma.American journal of cancer research · 2019Article
- Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids.Cancer letters · 2018Article
- microRNA involvement in the onset and progression of Barrett's esophagus: a systematic review.Oncotarget · 2018Review
- Response to TNF-α Is Increasing Along with the Progression in Barrett's Esophagus.Digestive diseases and sciences · 2017Article
- Rationale for targeting the Wnt signalling modulator Dickkopf-1 for oncology.British journal of pharmacology · 2017Review
- TERT Promoter Mutation in an Aggressive Cribriform Morular Variant of Papillary Thyroid Carcinoma.Endocrine pathology · 2017Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionWnt/β-catenin signaling activation has been reported only during the late steps of Barrett's esophagus (BE) neoplastic progression, but not in BE metaplasia, based on the absence of nuclear β-catenin. However, β-catenin transcriptional activity has been recorded in absence of robust nuclear accumulation. Thus, we aimed to investigate the Wnt/β-catenin signaling in nondysplastic BE.
methodsEsophageal tissues from healthy and BE patients without dysplasia were analyzed for Wnt target gene expression by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Esophageal squamous (EPC1-& EPC2-hTERT), BE metaplastic (CP-A), and adenocarcinoma (OE33) cell lines were characterized for Wnt activation by qRT-PCR, Western blot, and luciferase assay. Wnt activity regulation was examined by using recombinant Wnt3a and Dickkopf-1 (Dkk1) as well as Dkk1 short interfering RNA.
resultsWnt target genes (AXIN2, c-MYC, Cyclin D1, Dkk1) and Wnt3a were significantly upregulated in nondysplastic BE compared with squamous mucosa. Elevated levels of dephosphorylated β-catenin were detected in nondysplastic BE. Nuclear active β-catenin and TOPflash activity were increased in CP-A and OE33 cells compared with squamous cells. Wnt3a-mediated β-catenin signaling activation was abolished by Dkk1 in CP-A cells. TOPFlash activity was elevated following Dkk1 silencing in CP-A but not in OE33 cells. Dysplastic and esophageal adenocarcinoma tissues demonstrated further Dkk1 and AXIN2 overexpression.
conclusionsDespite the absence of robust nuclear accumulation, β-catenin is transcriptionally active in nondysplastic BE. Dkk1 overexpression regulates β-catenin signaling in BE metaplastic but not in adenocarcinoma cells, suggesting that early perturbation of Dkk1-mediated signaling suppression may contribute to BE malignant transformation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.